EE: Respiratory Quotient (RQ) (2013)


Frankenfield DC, Smith JS, Cooney RN. Accelerated nitrogen loss after traumatic injury is not attenuated by achievement of energy balance. J Parent Enteral Nutr. 1997; 21(6): 324-329.

Study Design:
Randomized controlled trial
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Quality Rating:
Neutral NEUTRAL: See Quality Criteria Checklist below.
Research Purpose:
  1. Examine the effect of energy balance on nitrogen balance and the catoblism of myofibrillar protein in multiply injured patients receiving parenteral nutrition with a fixed, high-protein content.


  • Steady state: A 30-min period when subject at rest and CV for O2consumption, CO2production, and minute ventilation was =10%.
    If resting period could not be maintained for 30 mins, a 5-min period with CV for VO2and VCO2and minute ventilatin = 5% was accepted.
  • Nonprotein calorie group: Nonprotein calorie intake balanced against measured energy expenditure
  • Total calorie intake: Caloric intake balanced against measured energy expenditure
  • Hypocaloric group: Nonprotein and total calorie intake was lower than measured energy expenditure.
Inclusion Criteria:
  1. Understand and give written consent
  2. Diseases in subjects that were allowed: expected required mechanical ventilation for at least 4 days
  3. Medications allowed:
Exclusion Criteria:
  1. Refusal to consent
  2. Not meeting inclusion criteria
  3. Diseases in subjects that were excluded: burn, spinal cord, or isolated brain injury
  4. Small bowel access for immediate enteral feeding
  5. FIO2>0.70 or air leaks
  6. Age <20 or >80 yrs
  7. Pregnancy, diabetes mellitus, renal insufficiency (i.e., serum Creatinine =1.5 mg/dL
  8. Steroid use.
Description of Study Protocol:

Parenteral nutrition was intitated within 48 hr of injury and infused continuously by means of a total nutrient admixture over 4-day period.

All grps received 1.7 gram amino acid/kg body weight; CHO (70% dextrose) was 4.5 gram/kg for nonprotein and total calorie groups and as close to 4.5 g/kg/day as possible in the hypocaloric group. Electrolytes, multi-vitamins were infused daily; vit K injections when indicated; 24-hr urine sample taken on day 4.


  • Ht measured? Yes
  • Wt measured? Yes
  • Fat-free mass measured? No


  • Monitored heart rate? Yes
  • Body temperature? Yes
  • Medications administered? Yes, IV medications and insulin if hyperglycemia developed
  • Serum prealbumin and transferring were measured at baseline and at study conclusion.

Resting energy expenditure

  • IC type: Delta-trac MB 101
  • Equipment of Calibration: Not specified
  • Coefficient of variation using std gases: No
  • Rest before measure (state length of time rested if available): Yes
  • Measurement length: 30 min
  • Steady state: yes, see above
  • Fasting length: no; parenteral initiated within 48 hours of injury
  • Exercise restrictions XX hr prior to test? not applicable
  • Room temp: ICU temperature
  • No. of measures within the measurement period: measured daily; n=4 meaures/pt
  • Were some measures eliminated? Yes; non-steady state
  • Were a set of measurements averaged? One-minute measures for either 30 min or 5 minutes
  • Coefficient of variation in subjects measures? No
  • Training of measurer? not specified
  • Subject training of measuring process? Yes, informed consent.


  • Total parenteral nutrition
  • Intervening factor:
Data Collection Summary:


  1. Nitrogen metabolism studies: 24 hr urine for urea, 3-methylhistidine, Nitrogen balance was calucated as difference b/t N-intake (amino acid intake/6.25) and total nitrogen production.
  2. Measured REE [(VO2 l/min), VCO2 (l/min; ml/kg/min), RQ, ventilation (l/min)].
  3. Independent variables of weight, height, age, , heart rate, max body temperature, leukocyte count, plasma glucose.

Blinding used:

Description of Actual Data Sample:

N=30 multiply-injured pt admitted to Level I trauma ICU

Nonpro cal grp (9 M; 1 F) (n=10)

  • Mean age, y: 42±23
  • Injury severity score: 27±11
  • Max body tem, C: 38.4±0.4

Total cal group (7 M; 3 F)

  • Mean age, y: 4±24
  • Injury severity score: 27±7
  • Max body tem, C: 38.5±0.9

Hypocalorie group (8 M; 2 F)

  • Mean age, y: 45±16
  • Injury severity score: 25±6
  • Max body tem, C: 38.0±0.5

Statistical tests

ANOVA to test for differences simultaneously among the 3 study groups; Tukey’s test with family error rate , P<0.05; Linear and multiple regression techniques were used to relate variables to one another.

Summary of Results:

There were no significant differences among the groups in total or nonprotein VO2 VCO2 RQ or energy expenditure.

  • Group mean RQ (±SD) by group was:
  • Nonprotein calorie group: 0.90±0.04
  • Total calorie group: 0.87±0.03
  • Hypocalorie group: 0.87±0.02
Author Conclusion:

As stated by the author in body of report: 

There does not appear to be consensus among clinicians regarding the definition of energy balance in critically ill patients. The results suggest that, in the acute setting, achievement of nonprotein or total energy balance does not prevent negative nitrogen balance or protein catabolism in critically ill multiple trauma patients. ”

“This study does not demonstrate or refute any of the potentially favorable outcomes of underfeeding, but does show that hypocaloric feeding promotes endogenous lipid mobilization without adversely affecting the aspects of protein metabolism measured.”

“ Two limitation of our study are small sample size increasing the possibility of thyp II error; However, reanalysis of data with alpha set at 0.15 (decreasing Beta) revealed no changes in the statistical significance among th feeding groups; Furthermore, actual differences among groups were quite small and of no clinical significance.
Funding Source:
University/Hospital: Pennsylvania State University
Reviewer Comments:


“Pre-planned research design chose a 4-day nutrient infusion period to conclude study before resolution of the catabolic response and avoiding metabolic complexities for pts entering into multiple organ dysfunction.”

IC measure had well-defined steady state and author describes ongoing monitoring throughout measure.


“Patients who are well-nourished before multiple-injury trauma receiving TPN during the acute phase of injury; unable to generalize to malnourished patients, pts with major burn or severe sepsis, or enteral fed patients.”

Unable to determine frequency of machine calibration; training of measurer is likely but not specified.

Quality Criteria Checklist: Primary Research
Relevance Questions
  1. Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) Yes
  2. Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? Yes
  3. Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? Yes
  4. Is the intervention or procedure feasible? (NA for some epidemiological studies) Yes
Validity Questions
1. Was the research question clearly stated? Yes
  1.1. Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? N/A
  1.2. Was (were) the outcome(s) [dependent variable(s)] clearly indicated? N/A
  1.3. Were the target population and setting specified? N/A
2. Was the selection of study subjects/patients free from bias? Yes
  2.1. Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? N/A
  2.2. Were criteria applied equally to all study groups? N/A
  2.3. Were health, demographics, and other characteristics of subjects described? N/A
  2.4. Were the subjects/patients a representative sample of the relevant population? N/A
3. Were study groups comparable? Yes
  3.1. Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) N/A
  3.2. Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? N/A
  3.3. Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) N/A
  3.4. If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? N/A
  3.5. If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) N/A
  3.6. If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? N/A
4. Was method of handling withdrawals described? Yes
  4.1. Were follow-up methods described and the same for all groups? N/A
  4.2. Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) N/A
  4.3. Were all enrolled subjects/patients (in the original sample) accounted for? N/A
  4.4. Were reasons for withdrawals similar across groups? N/A
  4.5. If diagnostic test, was decision to perform reference test not dependent on results of test under study? N/A
5. Was blinding used to prevent introduction of bias? No
  5.1. In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? N/A
  5.2. Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) N/A
  5.3. In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? N/A
  5.4. In case control study, was case definition explicit and case ascertainment not influenced by exposure status? N/A
  5.5. In diagnostic study, were test results blinded to patient history and other test results? N/A
6. Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? Yes
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  6.2. In observational study, were interventions, study settings, and clinicians/provider described? N/A
  6.3. Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? N/A
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? N/A
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  6.7. Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? N/A
  6.8. In diagnostic study, were details of test administration and replication sufficient? N/A
7. Were outcomes clearly defined and the measurements valid and reliable? No
  7.1. Were primary and secondary endpoints described and relevant to the question? N/A
  7.2. Were nutrition measures appropriate to question and outcomes of concern? N/A
  7.3. Was the period of follow-up long enough for important outcome(s) to occur? N/A
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? N/A
  7.5. Was the measurement of effect at an appropriate level of precision? N/A
  7.6. Were other factors accounted for (measured) that could affect outcomes? N/A
  7.7. Were the measurements conducted consistently across groups? N/A
8. Was the statistical analysis appropriate for the study design and type of outcome indicators? Yes
  8.1. Were statistical analyses adequately described and the results reported appropriately? N/A
  8.2. Were correct statistical tests used and assumptions of test not violated? N/A
  8.3. Were statistics reported with levels of significance and/or confidence intervals? N/A
  8.4. Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? N/A
  8.5. Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? N/A
  8.6. Was clinical significance as well as statistical significance reported? N/A
  8.7. If negative findings, was a power calculation reported to address type 2 error? N/A
9. Are conclusions supported by results with biases and limitations taken into consideration? Yes
  9.1. Is there a discussion of findings? N/A
  9.2. Are biases and study limitations identified and discussed? N/A
10. Is bias due to study's funding or sponsorship unlikely? Yes
  10.1. Were sources of funding and investigators' affiliations described? N/A
  10.2. Was the study free from apparent conflict of interest? N/A